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A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

The synthesis of aziridines—three-membered nitrogen-containing heterocycles—is achieved by a new method involving the electrochemical coupling of alkenes and amines, via a dicationic intermediate.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Foragers hunted small game locally and procured most large prey in riparian habitats and Afromontane grasslands to the southeast of the Kasitu Valley of northern Malawi, suggesting that migratory behavior in large grazers was absent, according to strontium isotopic analysis.

Azoles are important synthetic targets due to their diverse applications in areas ranging from human health to food security. Now it has been shown that the hydroazolation of alkenylthianthrenium salts provides a modular platform to access diverse, densely functionalized N-alkyl azole compounds with high N-regioselectivity.

Wang et al. present T cell receptor sequencing of serial tumor and blood samples from TIL-treated patients with non-small cell lung cancer, identifying tumor-reactive clonotypes expressing dysfunctional programs in patients lacking clinical benefit.

Zachary Lippman and colleagues report mutations in the tomato ortholog of CLV1 and a gene encoding a hydroxyproline O-arabinosyltransferase enzyme that modifies CLV3, both of which cause fasciated flowers and fruits owing to increased meristem size. They also find that a natural mutation in CLV3 was a major target of selection during tomato domestication.

Progressive supranuclear palsy is a devastating neurological disorder without treatment. Here, the authors leveraged omics data and model organisms to nominate, prioritize, and validate high-confidence candidate genes as therapeutic targets.

Variation in inflorescence architecture in plants affects reproductive success and agricultural yield. Zachary Lippman and colleagues report that the phenotype of the terminating flower (tmf) tomato mutant, the only known tomato mutant with single-flower inflorescence, is caused by a mutation affecting a nuclear protein that regulates known floral meristem identity complex members AN and FA to repress floral termination.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Leveraging enzymatic selectivity, a single reaction stream provides a single diastereomer of the cyclic dinucleotide MK-1454, a promising immune-oncology drug candidate, without the use of protecting groups or chiral auxiliaries.

Gene duplication and subsequent paralogue diversification are major obstacles to genotype-to-phenotype predictability.

A study developed genomic resources and efficient transformation in the orphan crop groundcherry, and managed to improve productivity traits by editing the orthologues of tomato domestication and improvement genes using CRISPR–Cas9.

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Genome-wide analyses of blood cell phenotypes derived from perturbations coupled with flow cytometry-based functional readouts identify loci associated with latent cellular traits, yielding insights into biological mechanisms underlying common diseases.

Alterations to the extracellular matrix have long been associated with cancer progression and therapeutic resistance. Schwörer et al. describe a mechanism whereby fibroblasts reroute metabolites to fuel the demands of collagen synthesis, leading to cancer progression.

Two types of magnetic order appear in metals, 'itinerant-electron' magnetism and 'local-moment' magnetism. A class of strongly correlated electron materials bridges these two extremes, with itinerant-electron magnetism reigning at low temperature and local-moment magnetism at high temperature. It has been a long-standing goal to quantitatively describe the transition between these two. This paper reports a simple semi-quantitative solution to the latter problem that provides a new framework for interpreting the physics of heavy electron materials.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The mechanical properties of tissues can be measured by deforming magnetically responsive microdroplets that are implanted in the tissue. Serwane et al. apply this method to study the mechanical properties of tissues in the living zebrafish embryo.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

A study of a stem cell receptor–ligand signaling module across tomato, maize and Arabidopsis identifies different genetic mechanisms of compensation that contribute to homeostasis.

Adoptive cell therapy with tumor-infiltrating lymphocytes in metastatic lung cancer patients is safe and elicits antitumor activity, including ongoing complete responses, in association with polyclonal T cell responses against tumor antigens.